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Background: The V2 receptor antagonist tolvaptan is prescribed to patients with autosomal dominant polycystic kidney disease to slow disease progression. Tolvaptan may alter BP via various acute and chronic effects. Methods: To investigate the magnitude and time course of the effect of tolvaptan use on BP, we conducted a post hoc study of the TEMPO 3:4 trial, which included 1445 patients with autosomal dominant polycystic kidney disease randomized 2:1 to tolvaptan or placebo for 3 years. We evaluated systolic and diastolic BP, mean arterial pressure, hypertension status, and use and dosing of antihypertensive drugs over the course of the trial. Results: At baseline, BP did not differ between study arms. After 3 weeks of tolvaptan use, mean body weight had decreased from 79.7 to 78.8 kg, and mean plasma sodium increased from 140.4 to 142.6 mmol/L (both P

Introduction In pivotal trials of patients with autosomal dominant polycystic kidney disease at risk of rapid progression, tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in early-to-moderate (TEMPO 3:4 [NCT00428948]) and moderate- to late-stage (REPRISE [NCT02160145]) chronic kidney disease (CKD). Discontinuation was less frequent in REPRISE (15.0%) than TEMPO 3:4 (23.0%), given that in REPRISE, only subjects who tolerated tolvaptan 60/30 mg daily initiated the double-blind phase. We evaluated whether the greater treatment effect in REPRISE was attributable to different completion rates. Methods We conducted post hoc analyses of TEMPO 3:4 and REPRISE completers, defined as subjects who took trial drug to the end of the treatment period in TEMPO 3:4 (3 years) or REPRISE (1 year). Efficacy (rate of change in eGFR for tolvaptan vs. placebo) was analyzed as in each trial. Subjects from TEMPO 3:4 and REPRISE were also matched by propensity score for age, gender, and baseline eGFR to explore potential additional determinants of treatment effect. Results The annualized tolvaptan treatment effect in TEMPO 3:4 completers (difference vs. placebo of 0.98 ml/min per 1.73 m2/y) and REPRISE completers (difference of 1.23) was similar to that of the respective total trial populations (TEMPO 3:4: 0.94; REPRISE: 1.27). The treatment effect of tolvaptan was also similar between matched subjects. Conclusion Greater treatment completion rate did not drive greater treatment effect in REPRISE. The more advanced CKD of REPRISE subjects may be more relevant. More rapid decline in kidney function in later-stage CKD enabled the effects of tolvaptan to be more easily discerned., Graphical abstract

Introduction In the Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease (ADPKD), the height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-α, is calculated by the equation [HtTKV at age t] = K(1+α/100)(t-A), where K = 150 and A = 0 are used in MIC. If eHTKV-α is nearly stable during a standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of the treatment effect on the HtTKV slope. Methods The constancy of eHTKV-α (A = 0 and K = 150) was evaluated using 453 placebo-assigned subjects in the Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 trial. A and K were sought out respectively by a converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-α from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-α from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4. Results In placebo-assigned subjects, eHTKV-α (A = 0 and K = 150) changed significantly from baseline at the third year. As regression lines of placebo-assigned subgroups converged around age 0, A was set as 0, which was confirmed by KUC. K = 130 was selected because of minimal change in eHTKV-α from baseline. The KUC validated the constancy of eHTKV-α (A = 0 and K = 130) but not that of eHTKV-α (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-α remained significantly lower than baseline for 3 years. Conclusions eHTKV-α (A = 0 and K = 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

Introduction Tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in subjects with autosomal dominant polycystic kidney disease (ADPKD) in TEMPO 3:4 and REPRISE trials. Tolvaptan effects in subjects with eGFR 15 to 24 ml/min per 1.73 m2 were not investigated. This post hoc analysis retrospectively investigated eGFR decline in REPRISE versus an open-label, phase 3b extension trial (open-label extension [OLE] NCT02251275) in subjects who received placebo in REPRISE and tolvaptan in OLE with eGFR 15 to 24 and 25 to 29 ml/min per 1.73 m2, respectively. Methods One data subset comprised subjects with OLE baseline eGFR 15 to 29 ml/min per 1.73 m2 who had received placebo in REPRISE and began tolvaptan in OLE. The second comprised subjects who had received tolvaptan in REPRISE and were matched to REPRISE placebo-treated subjects for REPRISE baseline characteristics. Annualized eGFR slopes in REPRISE versus OLE were compared within the REPRISE placebo (i.e., placebo vs. tolvaptan treatment) and tolvaptan (i.e., 2 periods of tolvaptan treatment) subsets. Results Mean annualized eGFR slopes (ml/min per 1.73 m2) during tolvaptan treatment in OLE versus placebo treatment in REPRISE were −3.4 versus −5.2 for subjects with OLE baseline eGFR 15 to 29 (difference, 1.7; P < 0.001), −3.6 versus −5.4 with baseline eGFR 15 to 24 (difference, 1.8; P < 0.001), and −3.3 versus −4.9 with baseline eGFR 25 to 29 (difference, 1.6; P < 0.001). In REPRISE tolvaptan subjects who continued tolvaptan in OLE, treatment effect was maintained (no difference between mean annualized eGFR slopes). Conclusion Initiating or maintaining tolvaptan therapy significantly delayed eGFR decline in subjects with baseline eGFR 15 to 24 and 25 to 29 ml/min per 1.73 m2., Graphical abstract

Background and Aims ADPKD is a progressive inherited disease that causes end-stage renal disease (ESRD) in ∼50% of the affected individuals by 60 years of age. TOL, a selective vasopressin V2-receptor antagonist, has been shown in randomized, placebo-controlled trials to slow the progression of renal function decline in ADPKD subjects with an eGFR of 25 mL/min/1.73m2 or higher. The efficacy and safety of TOL in subjects with lower eGFR remain understudied. This post-hoc analysis evaluated the efficacy and safety of TOL in subjects with stage 4 ADPKD (eGFR of Method This is a retrospective analysis of a subgroup of ADPKD subjects who enrolled in the TOL long-term open-label extension (OLE) trial (NCT02251275). Included subjects had a baseline eGFR of Results Of the 1,803 subjects enrolled, 159 (8.8%) subjects (76 in Subgroup 1 and 83 in Subgroup 2) met the selection criteria for analysis. Annualized eGFR change slopes for all subjects (n=148) were -5.28 (SE 0.27) in the control period and -3.16 (SE 0.30) in the treatment period with a treatment effect of 2.11 mL/min/1.73m2/year (95% CI 1.56, 2.66), p Conclusion This post-hoc analysis demonstrated that TOL significantly decreases the rate of eGFR decline in ADPKD subjects with stage 4 CKD, including those with an eGFR of

Quantum parametric mode sorting has been shown to enable photon counting with precise time gating and exceptional noise rejection that significantly exceeds what is possible with linear filters. While previous experimental demonstrations were in a collinear optical configuration, its response to off-axis scattering must be understood to apply it more broadly in remote sensing missions. To evaluate this prospect, we use a laboratory testbed to examine its performance for detecting photons at small angles, along both forward and backward directions, after passing through strongly scattering media. Our results find no measurable degradation in detecting noncollinear photons along both directions. This finding indicates that the key intra-pulse coherence essential to quantum parametric mode sorting is maintained at a small scattering angle, permitting its applications on a moving platform.

There are no guidelines for antibiotic prophylaxis for ureteral stent removal after kidney transplantation. We reviewed the charts of 277 adult kidney transplant recipients with ureteral stents transplanted at our center between September 2014 and December 2015 and investigated whether antibiotic prophylaxis for stent removal was associated with reduced incidence of urinary tract infections (UTI). We defined UTI as a urine culture ≥104 CFU/mL of bacterial isolates irrespective of symptoms. Primary outcome was the incidence of UTI within four weeks of stent removal. Among the 277 recipients, 199 (72%) were on sulfamethoxazole/trimethoprim (SMZ/TMP) as Pneumocystis jirovecii prophylaxis. At the time of ureteral stent removal, 56 recipients (20%) received additional antibiotic prophylaxis (ABX+) and 221 (80%) did not (ABX-). The difference in the incidence of UTI in the ABX(+) group (16%) and ABX(-) group (19%) was not statistically significant (P = 0.85). Variables independently associated with the development of UTI were recipient age (odds ratio [OR] 1.04, [95% confidence interval 1.01-1.07]) and UTI while stents were in situ (OR 3.9 [2.00-7.62]). Use of SMZ/TMP was protective (OR 0.35 [0.18-0.7]). Our study does not show a statistically significant benefit for additional antibiotic prophylaxis for ureteral stent removal. Antibiotic prophylaxis may be beneficial for recipients not on SMZ/TMP at the time of stent removal.

Space-based microwave radiometers (MRs) have a long history of providing critical inputs for retrieval algorithms that generate accurate estimates of geophysical properties of the Earth’s surface and atmosphere. Mission cost reduction pressure has led to increased use of small spacecraft (e.g. CubeSats and SmallSats) for scientific and operational Earth observation applications. The need for miniaturized MR electronics that fit into SmallSats and maintain performance poses a challenge for conventional MR technologies. Channel filters are one driver of MR size and weight. Microwave photonics (MWP) fabricated on silicon photonic integrated circuits (PICs) is one means to dramatically reduce the size of these filters enabling SmallSat platform integration and enhanced measurement capability. In this paper, we address the performance requirements for PICs to provide a viable path for low cost, size, weight and power (c-SWaP) MRs. We present experimental results of a silicon PIC filter development and a new electro-optic modulator (EOM) design that will integrate monolithically with these filters. The performance of an integrated MWP-based MR is modeled and compared to an operational MR. It is shown that the MWP design using the new EOM can provide radiometric performance comparable to conventional MRs but within a dramatically smaller sensor volume and in a purely silicon platform enabling low cost.

Magnetic resonance imaging (MRI) was used to investigate muscle rehabilitation following cast immobilization. The aim was to explore MRI as an imaging biomarker of muscle function. Sixteen patients completed an eight-week rehabilitation programme following six weeks of cast immobilization for an ankle fracture. MRI of the lower leg was performed at two-week intervals for 14 weeks. Total volume and anatomical cross-sectional areas at 70% of the distance from lateral malleolus to tibial tuberosity (ACSA) were measured for tibialis anterior (TA), medial and lateral gastrocnemius (GM and GL) and soleus (SOL). Pennation angle of muscle fascicules was measured at the same position in GM. Fractional fat/water contents and T2 relaxation times before and after exercise were calculated. Strength was measured as maximum isometric torque developed in plantar- and dorsi-flexion. Torque increased by (mean [SD]) 1.10 (0.32) N m day−1 in males, 0.74 (0.43) N m day−1 in females in plantar-flexion (0.9% of final strength p...

Surgical stress, corticosteroids, and mycophenolate may contribute to gastrointestinal ulcers/bleeding after kidney transplantation. Prophylactic acid suppression with H2RAs or PPIs is often utilized after transplantation, although unclear if truly indicated after early corticosteroid withdrawal (CSWD). PPIs have been associated with increased risks of Clostridium difficile infection (CDI), pneumonia, and acute rejection. This retrospective cohort study investigated benefits and risks of prolonged PPI use following kidney transplantation and included 286 kidney recipients undergoing CSWD within five d of transplant who were maintained on tacrolimus and mycophenolate mofetil/sodium. Patients on PPI before transplant, H2RA before/after transplant, and/or those with pre-transplant GI complications were excluded. A total of 171 patients received PPI>30 d, mean duration 287 ± 120 d (PPI group); 115 patients were not maintained on acid suppression (No-PPI group). GI ulceration and bleeding events were rare in PPI group (1.2% and 2.3%, respectively) and not observed in No-PPI group (p = NS). The incidence of infectious or hematological complications was not significantly different between groups. The PPI group experienced more biopsy-proven acute rejection (9.4% vs. 2.6%, p = 0.03). No direct benefit was observed with PPI in reducing the incidence of GI ulcers and bleeding events in kidney transplant recipients undergoing early CSWD. Further studies are needed to investigate the association of PPI and acute rejection.

Purpose: To investigate MRI biomarkers of muscle atrophy during cast immobilization of the lower leg. Materials and Methods: Eighteen patients (8 male, 10 female), who had one lower leg immobilized in a cast, underwent 3.0 Tesla (T) MR imaging 5, 8, 15, 29, and 43 days after casting. Measurements were made on both lower legs of total muscle volume. Cross-sectional area (CSA), fractional water content, and T2 were measured in tibialis anterior (TA), gastrocnemius medialis (GM) and lateralis (GL) and soleus (SOL). Fiber pennation angle was measured in GM. Results: Total muscle volume decreased by 17% (P < 0.001) over the 6 weeks of immobilization. The greatest loss in CSA (mean[SD]) was seen in GM (−23.3(8.7)%), followed by SOL (−19.0(9.8)%), GL (−17.1(6.5)%), and TA (−10.7(5.9)%). Significant reductions of CSA were also detectable in the contra-lateral leg. T2 increased in all muscles: TA 27.0(2.5) ms to 29.6(2.8) ms (P < 0.001), GM 34.6(2.9) ms to 39.8(5.4) ms (P < 0.001) and SOL 34.4 (2.9) ms to 44.9(5.9) ms (P < 0.001). Small reductions were found in fractional water content. Pennation angle decreased in the cast leg (P < 0.001). Conclusion: Quantitative MR imaging can detect and monitor progressive biochemical and biophysical changes in muscle during immobilization. J. Magn. Reson. Imaging 2012;35:686-695. © 2011 Wiley Periodicals, Inc.

Summary Objective The sensitivity to change of quantitative analysis of cartilage in knee osteoarthritis using magnetic resonance imaging (MRI) is compromised by the spatial heterogeneity of cartilage loss. We explore whether extended (medial–lateral) "ordered values" (OVs) are superior to conventional approaches of analyzing subregional cartilage thickness loss and to radiography, in differentiating rates of progression in knees with and without joint space narrowing (JSN). Methods 607 Osteoarthritis Initiative (OAI) participants (308 without and 299 with baseline JSN at baseline) were studied over 12 months. Subregional femorotibial cartilage loss was determined in all knees, and changes in minimum joint space width (mJSW) in a subset of 290 knees. Subregional thickness changes in medial and lateral tibial and femoral cartilages were sorted in ascending order (OV1-16). A Wilcoxon rank-sum test was used to compare rates of change in knees with and without JSN. Results JSN-knees displayed greater cartilage loss than those without JSN, with minimal P -values of 0.008 for femorotibial subregions, 3.3×10 −4 for medial OV1, and 5.4×10 −7 for extended (medial and lateral) OV1. mJSW measurements ( n =290) did not discriminate between longitudinal rates of change in JSN vs no-JSN knees ( P =0.386), whereas medial OV1 ( P =5.1×10 −4 ) and extended OV1 did ( P =2.1×10 −5 ). Conclusion Extended OVs showed higher sensitivity to detecting differences in longitudinal rates of cartilage loss in knees with and without baseline JSN than anatomical (sub)regions and radiography. The OV technique also circumvents challenges of selecting particular regions "a priori" in clinical trials and may thus provide a powerful tool in studying risk factors or treatment efficacy in osteoarthritis.

Summary Objective To compare femorotibial cartilage thickness changes over a 2- vs a 1-year observation period in knees with radiographic knee osteoarthritis (OA). Methods One knee of 346 Osteoarthritis Initiative (OAI) participants was studied at three time points [baseline (BL), year-1 (Y1), year-2 (Y2) follow-up]: 239 using coronal fast low angle shot (FLASH) and 107 using sagittal double echo at steady state (DESS) MR imaging. Changes in cartilage thickness were assessed in femorotibial cartilage plates and subregions, after manual segmentation with blinding to time-point. Results The standardized response mean (SRM) of total joint cartilage thickness over 2 years was modestly higher than over 1 year (FLASH: −0.44 vs −0.32/−0.28 [first/second year]; DESS: −0.42 vs −0.39/−0.18). For the subregion showing the largest change per knee (OV1), the 2-year SRM was similar or lower (FLASH: −1.20 vs −1.22/−1.61; DESS: −1.38 vs −1.64/−1.51) than the 1-year SRM. The changes in total joint cartilage thickness were not significantly different in the first and second year (FLASH: −0.8% vs −0.7%; DESS: −1.3% vs −0.8%) and were negatively correlated. Analysis of smallest detectable changes (SDCs) revealed that only few participants displayed significant progression in both consecutive periods. The location of the subregion contributing to OV1 in each knee was highly inconsistent between the first and second year observation period. Conclusions The SRM of region-based cartilage thickness change in OA is modestly larger following a 2-year vs a 1-year observation period, while it is relatively similar when an OV-approach is chosen. Structural progression displays strong temporal and spatial heterogeneity at an individual knee level that should be considered when planning clinical trials.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of online support group (OSG) use by those with chronic health problems and to identify characteristics associated with use of OSGs and face-to-face groups. METHODS: 6, 795 Californians living with chronic health problems were asked to describe OSG use, face-to-face support group use, and frequency/perceived benefit of support group use. RESULTS: 16% had used a face-to-face group for health, and 1.8% reported having used an OSG. OSG use was associated with depression/anxiety (OR = 3.51), stroke (OR = 3.03), diabetes (OR = 2.96), cancer (OR = 2.86), and arthritis (OR = 2.52). Use of OSGs was also associated with greater education (OR = 12.2), higher income (OR = 3.1), use of complementary/alternative therapies (OR = 5.2), and worse health status (OR = 3.1). Those with asthma (OR = 0.4), over age 65 (OR = 0.2), and Latinos (OR = 0.2) were less likely to use OSGs. CONCLUSION: Prevalence of use of OSGs for those with chronic health conditions is low, but internet-based health-related services have potential to increase the reach of support services for those living with chronic conditions.

Hyponatremia (serum sodium [Na+] concentration136 mmol/L) is a prevalent and potentially life-threatening medical comorbidity for schizophrenic patients. No definitive pharmacological treatments have been established. Tolvaptan (OPC-41061), an oral non-peptide V2-receptor antagonist, was recently shown to correct hyponatremia in a diverse population of 448 hyponatremic patients. Efficacy in a sub-set of 19 schizophrenic patients with idiopathic hyponatremia included in that sample is specifically examined.Nineteen subjects were randomly assigned to receive placebo (n = 12) or tolvaptan (n = 7) once daily for 30 days. Dosage adjustment was based on serum Na+ changes, initially 15 mg, titratable to 30 or 60 mg. The average daily area under the curve (AUC) changes in serum Na+ from baseline to Day 4 and Day 30 were co-primary end points.Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 (p = .0055) and at Day 30 (p.0001). Two subjects receiving tolvaptan (28.6%) became dehydrated and experienced hypotension, and five subjects receiving placebo (41.7%) experienced symptoms associated with dilutional hyponatremia.These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia in schizophrenic patients. Clinicians are advised to carefully monitor fluid status especially at the beginning of treatment to prevent dehydration.

Researchers have found that immigrants in the United States gradually relinquish cultural practices and adopt health behaviors similar to native born individuals as they acculturate. Few studies have looked at acculturation and Complementary and Alternative Medicine (CAM) use, particularly ethnic forms of CAM. This study uses data from the 2001 California Health Interview Survey-Complementary and Alternative Medicine (CHIS-CAM) supplement to estimate the prevalence of CAM provider use among Mexican- and Asian- Americans and examine the relationship of acculturation on use. Multinomial logistic regression models were used to predict the probability of provider use based on socio-demographic variables, health status and acculturation. Mexican- and Asian- Americans who have spent more time in the US were more likely to use chiropractors or massage therapists compared to no CAM provider. Both groups were less likely to use ethnic-specific CAM providers with more time in the US compared to chiropractors or massage therapists.

Soliton self-frequency shift (SSFS), a consequence of Raman self-pumping that continuously red-shifts a soliton pulse, has been widely studied recently for applications to fiber-based sources and signal processing. In this paper, the fundamentals of SSFS are reviewed. Various fiber platforms for SSFS (single-mode fiber, microstructured fiber, and higher order mode fiber) are presented and experimental SSFS demonstrations in these fibers are discussed. Observation of Cerenkov radiation in fibers exhibiting SSFS is also presented. A number of interesting applications of SSFS, such as wavelength-agile lasers, analog-to-digital conversion, and slow light, are briefly discussed.

Oceanographic lidar profiles measured in an aerial survey were compared with in situ measurements of water optical properties made from a surface vessel. Experimental data were collected over a two-week period in May 2010 in East Sound, Washington. Measured absorption and backscatter coefficients were used with the volume-scattering function in a quasi-single-scattering model to simulate an idealized lidar return, and this was convolved with the measured instrument response to accurately reproduce the measured temporal behavior. Linear depth-dependent depolarization from the water column and localized depolarization from scattering layers are varied to fine tune the simulated lidar return. Sixty in situ measurements of optical properties were correlated with nearly collocated and coincident lidar profiles; our model yielded good matches (±3 dB to a depth of 12 m) between simulated and measured lidar profiles for both uniform and stratified waters. Measured attenuation was slightly higher (5%) than diffuse attenuation for the copolarized channel and slightly lower (8%) for the cross-polarized channel.

We design and implement a novel class of highly precise network instrumentation, capable of the first-ever capture of exact packet timings of network traffic. Our instrumentation — combining real-time physics test equipment with off-line postprocessing software — prevents interference with the system under test, provides reproducible measurements by eliminating non-deterministic error, and uses transparent and ubiquitous lab equipment and open-source software for ease of replication. We use our technique to perform in-situ observations of 10 Gigabit Ethernet packets in flight on optical fiber, showing improvements in timing precision of two to six orders of magnitude over existing methods of measurement, which generally employ software on commodity computer endpoints of network paths.

We use the time-lens concept to demonstrate a new scheme for synchronization of two pulsed light sources for biological imaging. An all fiber, 1064 nm time-lens source is synchronized to a picosecond solid-state Ti: Sapphire mode-locked laser by using the mode-locked laser pulses as the clock. We demonstrate the application of this synchronized source for CARS and SRS imaging by imaging mouse tissues. Synchronized two wavelength pulsed source is a major technical difficulty for CARS and SRS imaging. The time-lens source demonstrated here may provide an all-fiber, user friendly alternative for future SRS imaging.

We characterize the focusing properties of the LP02 mode in a typical multiphoton microscope. Under varying back-aperture filling conditions, we measure vastly different point spread functions, including a null at the focus.

Objective To identify structural differences in total subchondral bone area (tAB) and cartilage thickness between healthy reference knees and knees with radiographic osteoarthritis (OA). Methods Baseline magnetic resonance images from 1 knee of 1,003 Osteoarthritis Initiative participants were studied: 112 healthy reference knees without radiographic OA, symptoms, or risk factors; 70 preradiographic OA knees (calculated Kellgren/Lawrence [K/L] grade 0/1); and 821 radiographic OA knees (calculated K/L grade ≥2). Means and standard (Z) scores (SD unit differences compared with normal subjects) of the tAB and regional cartilage thickness were assessed in the weight-bearing femorotibial joint and compared between groups. Results In men, tAB was 8.2% larger in preradiographic OA knees and 6.6%, 8.1%, and 8.5% larger in calculated K/L grade 2, 3, and 4 radiographic OA knees, respectively, than in reference knees. In women, the differences were +6.8%, +7.3%, +9.9%, and +8.1%, respectively. The external medial tibia showed the greatest reduction in cartilage thickness (Z scores −5.1/−5.6 in men/women) with Osteoarthritis Research Society International medial joint space narrowing (JSN) grade 3, and the external lateral tibia (Z scores −6.0 for both sexes) showed the greatest reduction with lateral JSN grade 3. In all subregions of end-stage radiographic OA knees, ≥25% of the average normal cartilage thickness was maintained. An overall trend toward thicker cartilage was found in preradiographic OA and calculated K/L grade 2 knees, especially in the external central medial femur. Conclusion tABs were larger in preradiographic OA and radiographic OA knees than in healthy reference knees, and the difference did not become larger with higher calculated K/L grades. Specific subregions with substantial cartilage thickening or thinning were identified in pre-, early, and late radiographic OA.

We demonstrate an all-fiber, 2-ps, 1063-nm source using time-lens compression of a continuous-wave laser, with variable repetition rates, pulse sequence, and alternating pulse amplitude. We demonstrate Cerenkov radiation in a higher-order-mode fiber using the source.

Objective To study the longitudinal rate of (and sensitivity to) change of knee cartilage thickness across defined stages of radiographic osteoarthritis (OA), specifically healthy knees and knees with end-stage radiographic OA. Methods One knee of 831 Osteoarthritis Initiative participants was examined: 112 healthy knees, without radiographic OA or risk factors for knee OA, and 719 radiographic OA knees (310 calculated Kellgren/Lawrence [K/L] grade 2, 300 calculated K/L grade 3, and 109 calculated K/L grade 4). Subregional change in thickness was assessed after segmentation of weight-bearing femorotibial cartilage at baseline and 1 year from coronal magnetic resonance imaging (MRI). Regional and ordered values (OVs) of change were compared by baseline radiographic OA status. Results Healthy knees displayed small changes in plates and subregions (±0.7%; standardized response mean [SRM] ±0.15), with OVs being symmetrically distributed close to zero. In calculated K/L grade 2 knees, changes in cartilage thickness were small (

Using time-lens compression in a loop configuration, we generate 516 fs pulses at 3.5 nJ pulse energy from a continuous-wave 1.55 mum source without mode locking. Just as a spatial lens can expand or focus a beam in space, so can a time-lens broaden or compress a pulse in time. By placing a time-lens in a loop, we maximize the efficiency of bandwidth generation by using one time-lens driven at low power to emulate a stack of many lenses. Our system is compact, is all fiber, and allows large tuning of the repetition rate and continuous tuning of the pulse width and center wavelength.

We generate 516 fs pulses at 3.5 nJ energy from a continuous wave 1.55 mum source without mode-locking. Our system is compact, all-fiber, and allows continuous tuning of pulse width and center wavelength.

We demonstrate a method of generating short pulses at 1350 nm by exciting Cerenkov radiation in a higher-order-mode fiber with a 1064 nm femtosecond fiber laser. We measure a 106 fs, 0.66 nJ output pulse. Cerenkov radiation in fibers allows for energy transfer between a soliton and a dispersive wave, providing an effective and engineerable platform to shift the wavelength of a femtosecond source. With appropriate design of the higher-order-mode fiber, this method of generating short pulses at 1350 nm can be extended to other wavelengths and to higher pulse energies.

We demonstrate soliton self-frequency shift of more than 12% of the optical frequency in a higher-order mode solid, silica-based fiber below 1300nm. This new class of fiber shows great promise for supporting Raman-shifted solitons below 1300nm in intermediate energy regimes of 1 to 10nJ that cannot be reached by index-guided photonic crystal fibers or air-core photonic bandgap fibers. By changing the input pulse energy of 200fs pulses from 1.36 to 1.63nJ we observe Raman-shifted solitons between 1064 and 1200nm with up to 57% power conversion efficiency and compressed output pulse widths less than 50fs. Furthermore, due to the dispersion characteristics of the HOM fiber, we observe redshifted Cerenkov radiation in the normal dispersion regime for appropriately energetic input pulses.

Objective Joint injury in young adults leads to an increased risk of developing osteoarthritis (OA) later in life. This study was undertaken to determine if injurious mechanical compression of cartilage explants results in changes at the level of gene transcription that may lead to subsequent degradation of the cartilage. Methods Cartilage was explanted from the femoropatellar groove of newborn calves. Levels of messenger RNA encoding matrix molecules, proteases, their natural inhibitors, transcription factors, and cytokines were assessed in free swelling control cultures as compared with cartilage cultures at 1, 2, 4, 6, 12, and 24 hours after application of a single injurious compression. Results Gene-expression levels measured in noninjured, free swelling cartilage varied over 5 orders of magnitude. Matrix molecules were the most highly expressed of the genes tested, while cytokines, matrix metalloproteinases (MMPs), aggrecanases (ADAMTS-5), and transcription factors showed lower expression levels. Matrix molecules showed little change in expression after injurious compression, whereas MMP-3 increased approximately 250-fold, ADAMTS-5 increased approximately 40-fold, and tissue inhibitor of metalloproteinases 1 increased approximately 12-fold above the levels in free swelling cultures. Genes typically used as internal controls, GAPDH and beta-actin, increased expression levels approximately 4-fold after injury, making them unsuitable for use as normalization genes in this study. The expression levels of tumor necrosis factor alpha and interleukin-1beta, cytokines known to be involved in the progression of OA, did not change in the chondrocytes after injury. Conclusion Changes in the level of gene expression after mechanical injury are gene specific and time dependent. The quantity of specific proteins may be altered as a result of these changes in gene expression, which may eventually lead to degradation at the tissue level and cause a compromise in cartilage structure and function.

The effect of two-photon absorption on DPSK and OOK transmission is analyzed by simulation. DPSK is found to have an advantage over OOK in both Q and eye closure penalty for multi-channel WDM transmissions.

A dual-polarization lidar and photography are used to sense internal waves in West Sound, Orcas Island, Washington, from a small aircraft. The airborne lidar detected a thin plankton layer at the bottom of the upper layer of the water, and this signal provides the depth of the upper layer, amplitude of the internal waves, and the propagation speed. The lidar is most effective when the polarization filter on the receiver is orthogonal to the transmitted light, but this does not depend significantly on whether the transmitted light is linearly or circularly polarized. The depolarization is greater with circular polarization, and our results are consistent with a single parameter Mueller scattering matrix. Photographs of the surface manifestation of the internal waves clearly show the propagation direction and width of the phase fronts of the internal waves, even though the contrast is low (2%). Combined with the lidar profile, the total energy of the internal wave packet was estimated to be 9 MJ. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). (DOI: 10.1117/1.JRS.6.063611)

We use the time-lens concept to demonstrate a new scheme for synchronization of two pulsed light sources for biological imaging. An all fiber, 1064 nm time-lens source is synchronized to a picosecond solid-state Ti: Sapphire mode-locked laser by using the mode-locked laser pulses as the clock. We demonstrate the application of this synchronized source for CARS and SRS imaging by imaging mouse tissues. Synchronized two wavelength pulsed source is an important technical difficulty for CARS and SRS imaging. The time-lens source demonstrated here may provide an all fiber, user friendly alternative for future SRS imaging.

We demonstrate generation of Cerenkov radiation at 850 nm in a higher-order-mode (HOM) fiber. The LP02 mode in this solid, silica-based fiber has anomalous dispersion from 690 nm to 810 nm. Cerenkov radiation with 3 nJ pulse energy is generated in this module, exhibiting 60% energy conversion efficiency from the input. The HOM fiber provides a valuable fiber platform for nonlinear wavelength conversion with pulse energies in-between index-guided silica-core photonic crystal fibers and air-core photonic bandgap fibers.

We demonstrate tuning of the output spectrum of an HOM fiber module by changing the dispersion curve. Spectral feature wavelengths can be changed systematically by changing the location of the zero-dispersion wavelength.

We demonstrate a method of generating femtosecond pulses at 1350 nm by exciting Cherenkov radiation in a higher-order-mode fiber with a 1064 nm source. We measure a 134 fs, 0.66 nJ output pulse.